Materiały źródłowe

• #1 The molecular pathogenesis of head and neck cancer

  https://pmc.ncbi.nlm.nih.gov/articles/PMC3138532/

  Head and neck cancer arises from a series of molecular alterations progressive from dysplasia to carcinoma in situ, and finally invasive carcinoma. […] There are genetic alterations in pre-cancerous cells that contribute to transformation. The accumulation of these alterations facilitates tumor development. Additionally, the tumor microenvironment enables tumor progression. The cooperative effect of molecular alterations in the tumor cells and compensatory microenvironment changes enable tumors to invade and metastasize. […] This review will describe the pathogenesis of head and neck cancer with an emphasis on the genetic and molecular alterations that characterize HNSCC cells and surrounding stroma in the tumor microenvironment. Targeting molecular interactions between stromal cells and tumor cells may abrogate tumor progression.

• #2 Head and neck cancer: pathogenesis and targeted therapy

  https://pmc.ncbi.nlm.nih.gov/articles/PMC11338281/

  Head and neck cancer (HNC) is a highly aggressive type of tumor characterized by delayed diagnosis, recurrence, metastasis, relapse, and drug resistance. The occurrence of HNC were associated with smoking, alcohol abuse (or both), human papillomavirus infection, and complex genetic and epigenetic predisposition. […] In this review, we summarize the pathogenesis of HNC, including genetic and epigenetic changes, abnormal signaling pathways, and immune regulation mechanisms, along with all potential therapeutic strategies such as molecular targeted therapy, immunotherapy, gene therapy, epigenetic modifications, and combination therapies. […] Current clinical treatment of HNC. Tobacco, alcohol, viral infection, genomic changes, head and neck X-ray exposure, and poor oral hygiene are the main causes of HNC.

• #3 Head and neck cancer: pathogenesis and targeted therapy

  https://pmc.ncbi.nlm.nih.gov/articles/PMC11338281/

  Head and neck cancer (HNC) is a highly aggressive type of tumor characterized by delayed diagnosis, recurrence, metastasis, relapse, and drug resistance. The occurrence of HNC were associated with smoking, alcohol abuse (or both), human papillomavirus infection, and complex genetic and epigenetic predisposition. […] In this review, we summarize the pathogenesis of HNC, including genetic and epigenetic changes, abnormal signaling pathways, and immune regulation mechanisms, along with all potential therapeutic strategies such as molecular targeted therapy, immunotherapy, gene therapy, epigenetic modifications, and combination therapies. […] Current clinical treatment of HNC. Tobacco, alcohol, viral infection, genomic changes, head and neck X-ray exposure, and poor oral hygiene are the main causes of HNC.

• #4 Head and neck squamous cell carcinoma | Nature Reviews Disease Primers

  https://www.nature.com/articles/s41572-020-00224-3

  Most head and neck cancers are derived from the mucosal epithelium in the oral cavity, pharynx and larynx and are known collectively as head and neck squamous cell carcinoma (HNSCC). […] Oral cavity and larynx cancers are generally associated with tobacco consumption, alcohol abuse or both, whereas pharynx cancers are increasingly attributed to infection with human papillomavirus (HPV), primarily HPV-16. […] Thus, HNSCC can be separated into HPV-negative and HPV-positive HNSCC. […] Despite evidence of histological progression from cellular atypia through various degrees of dysplasia, ultimately leading to invasive HNSCC, most patients are diagnosed with late-stage HNSCC without a clinically evident antecedent pre-malignant lesion. […] Elucidation of the molecular genetic landscape of HNSCC over the past decade has revealed new opportunities for therapeutic intervention. […] Ongoing efforts aim to integrate our understanding of HNSCC biology and immunobiology to identify predictive biomarkers that will enable delivery of the most effective, least-toxic therapies.

• #5 ETIOPATHOGENESIS OF HEAD AND NECK CANCER.pptx

  https://www.slideshare.net/slideshow/etiopathogenesis-of-head-and-neck-cancerpptx/255463171

  Mechanism of Carcinogenesis Induce cp450 systems – formation of electrophilic DNA Adducts Miscoding at DNA Replication – cause G:A and G:T mutations, Inactivation of P53, Activation of KRAS Nicotine – not a carcinogen in itself. […] The International Agency for Research on Cancer (IARC), Lyons, France has classified both cigarette smoke and smokeless tobacco as Group 1 carcinogens. Identified 72 measurable carcinogens in cigarette smoke Group 1 (carcinogenic to humans) 2A (probably carcinogenic to humans) 2B (possibly carcinogenic to humans). […] Alcohol Second most important risk factor 75% of HNSCC, particularly cancers of the oral cavity, oropharynx, larynx and hypopharynx. A case-control study( Bruguere et al ) -a relative risk (adjusted for tobacco) in individuals with an alcohol consumption of 100160 g/day (12.520 units/day ) -13.5 for oral carcinoma -15.2 for cancers of the oropharynx -28.6 for the hypopharynx.

• #6 The Molecular Pathogenesis of Head and Neck Cancer – Clinical Tree

  https://clinicalpub.com/the-molecular-pathogenesis-of-head-and-neck-cancer/

  Head and neck squamous cell carcinoma (HNSCC) arises in the oral cavity, oropharynx, hypopharynx, and larynx. […] Tobacco use and alcohol consumption are the two most important risk factors for the development of HNSCC, and their contributions to risk are synergistic. […] The well-documented histological progression of HNSCC from oral leukoplakia through progressive phases of hyperplasia, dysplasia, carcinoma in situ, and ultimately invasive carcinoma is believed to correspond with the accumulation of genetic alterations. […] In HNSCC, one of the earliest initiating events is likely the clonal proliferation of precancerous cells with TP53 mutations. […] Recently, whole-exome sequencing studies of HNSCC have begun to reveal the genetic underpinnings of this disease. […] These data, in combination with previous genomic analyses, have identified the most commonly mutated genes in HNSCC as outlined in Table 33-1.

• #7 Pathogenetic Action of Viruses in Head and Neck Cancer | IntechOpen

  https://www.intechopen.com/online-first/1200317

  The early oncogenes E6 and E7, for instance, are overexpressed when HPV DNA is incorporated into host cells, inactivating the tumor suppressor proteins p53 and Rb, respectively. […] About 70% of oropharyngeal malignancies (OPCs) in the US are caused by HPV, and the incidence of HPV-associated HNCs, particularly oropharyngeal squamous cell carcinoma (OPSCC), is rising sharply. […] Different HNC subtypes have distinct molecular fingerprints and viral profiles that indicate different biological activities and treatment responses. Understanding how oncogenic viruses and host factors interact is essential for creating tailored treatment plans that effectively stop the progression of HNC while lowering treatment-associated morbidity. […] The mechanisms by which oncogenic viruses induce oncogenic transformation vary, but all have important common features. For example, a virus particle is capable of bringing about transformation. All or part of the viral genome remains in the transformed cells and this genome is expressed in these cells. Transformation is a result of the degeneration of normal cellular growth signals.

• #8 Head and neck cancer: pathogenesis and targeted therapy

  https://pmc.ncbi.nlm.nih.gov/articles/PMC11338281/

  Head and neck cancer (HNC) is a highly aggressive type of tumor characterized by delayed diagnosis, recurrence, metastasis, relapse, and drug resistance. The occurrence of HNC were associated with smoking, alcohol abuse (or both), human papillomavirus infection, and complex genetic and epigenetic predisposition. […] In this review, we summarize the pathogenesis of HNC, including genetic and epigenetic changes, abnormal signaling pathways, and immune regulation mechanisms, along with all potential therapeutic strategies such as molecular targeted therapy, immunotherapy, gene therapy, epigenetic modifications, and combination therapies. […] Current clinical treatment of HNC. Tobacco, alcohol, viral infection, genomic changes, head and neck X-ray exposure, and poor oral hygiene are the main causes of HNC.

• #9 Head and neck squamous cell carcinoma | Nature Reviews Disease Primers

  https://www.nature.com/articles/s41572-020-00224-3

  Most head and neck cancers are derived from the mucosal epithelium in the oral cavity, pharynx and larynx and are known collectively as head and neck squamous cell carcinoma (HNSCC). […] Oral cavity and larynx cancers are generally associated with tobacco consumption, alcohol abuse or both, whereas pharynx cancers are increasingly attributed to infection with human papillomavirus (HPV), primarily HPV-16. […] Thus, HNSCC can be separated into HPV-negative and HPV-positive HNSCC. […] Despite evidence of histological progression from cellular atypia through various degrees of dysplasia, ultimately leading to invasive HNSCC, most patients are diagnosed with late-stage HNSCC without a clinically evident antecedent pre-malignant lesion. […] Elucidation of the molecular genetic landscape of HNSCC over the past decade has revealed new opportunities for therapeutic intervention. […] Ongoing efforts aim to integrate our understanding of HNSCC biology and immunobiology to identify predictive biomarkers that will enable delivery of the most effective, least-toxic therapies.

• #10 The molecular pathogenesis of head and neck cancer

  https://pmc.ncbi.nlm.nih.gov/articles/PMC3138532/

  Head and neck cancer arises from a series of molecular alterations progressive from dysplasia to carcinoma in situ, and finally invasive carcinoma. […] There are genetic alterations in pre-cancerous cells that contribute to transformation. The accumulation of these alterations facilitates tumor development. Additionally, the tumor microenvironment enables tumor progression. The cooperative effect of molecular alterations in the tumor cells and compensatory microenvironment changes enable tumors to invade and metastasize. […] This review will describe the pathogenesis of head and neck cancer with an emphasis on the genetic and molecular alterations that characterize HNSCC cells and surrounding stroma in the tumor microenvironment. Targeting molecular interactions between stromal cells and tumor cells may abrogate tumor progression.

• #11 The Molecular Pathogenesis of Head and Neck Cancer | Clinical Gate

  https://clinicalgate.com/the-molecular-pathogenesis-of-head-and-neck-cancer/

  The Field Cancerization Theory is defined as the presence of one or more mucosal areas consisting of epithelial cells with cancer-associated genetic or epigenetic alterations. […] Additional genetic changes are needed to transform a field into a carcinoma. […] Studies attempting to identify specific genetic characteristics that determine the risk of a field developing into cancer have shown that genetic changes at chromosome 9p, decreased cytokeratin 4 expression, and decreased cornulin expression are potential biomarkers. […] Mutation of TP53 is the earliest and most frequent mutation event observed in HPV-negative HNSCC. […] In a large portion of HNSCC without somatic TP53 mutations, the activity of p53 is compromised by other mechanisms, including E6 expression in HPV(+) cancers, which inactivates p53, and overexpression and/or amplification of MDM2, which promotes the degradation of p53.

• #12 Mutant p53 in head and neck squamous cell carcinoma: Molecular mechanism of gain‑of‑function and targeting therapy (Review)

  https://www.spandidos-publications.com/10.3892/or.2023.8599

  Head and neck squamous cell carcinoma (HNSCC) is one of the most widespread malignancies worldwide. p53, as a transcription factor, can play its role in tumor suppression by activating the expression of numerous target genes. However, p53 is one of the most commonly mutated genes, which frequently harbors missense mutations. Most p53 mutations in HNSCC are missense mutations and the mutation rate of p53 reaches 65-85%. p53 mutation not only inhibits the tumor suppressive function of p53 but also provides novel functions to facilitate tumor recurrence, called gain-of-function (GOF). The present study focused on the prevalence and clinical relevance of p53 mutations in HNSCC, and further described how mutant p53 accumulates. Moreover, mutant p53 in HNSCC can interact with proteins, RNA, and exosomes to exert effects on proliferation, migration, invasion, immunosuppression, and metabolism. Finally, several treatment strategies have been proposed to abolish the tumor-promoting function of mutant p53; these strategies include reactivation of mutant p53 into wild-type p53, induction of mutant p53 degradation, enhancement of the synthetic lethality of mutant p53, and treatment with immunotherapy. Due to the high frequency of p53 mutations in HNSCC, a further understanding of the mechanism of mutant p53 may provide potential applications for targeted therapy in patients with HNSCC.

• #13 Head & Neck Cancers | OncologyPRO

  https://oncologypro.esmo.org/education-library/esmo-books/essentials-for-clinicians/head-neck-cancers/pathogenesis

  Transformation of normal mucosa into invasive HNSCC follows a molecular progression model of multistep carcinogenesis. […] Loss of genetic material from chromosome region 9p21 and inactivation of p16 tumour suppression gene are the earliest alterations identified at transition to hyperplastic mucosa. […] Subsequent transition to dysplasia is characterised by loss of 3p and 17p and by p53 inactivation. Loss of 11q, 13q and 14q precedes transition to carcinoma in situ. […] Loss of 6p, 8p and 4q is identified during transformation to invasive HNSCC. Tobacco-related HNSCC is associated with mutation of p53 and downregulation of p16 protein. […] Leukoplakia and erythroplakia are the precursors of invasive HNSCC in the oral mucosa. […] Field carcinogenesis refers to carcinogen distribution over large areas in upper aerodigestive tracts, due to continuous exposure, rendering mucosa a potential site for cancer.

• #14

  https://www.jci.org/articles/view/59889

  Recent advances in our understanding of the molecular pathogenesis of HNSCC were provided by whole-exome sequencing conducted on a total of approximately 100 HNSCC specimens. […] This work, together with a large body of previous genomic and functional analyses of HNSCC, highlights the relatively small number of oncogenes targeted by activating mutations and supports the fundamental roles of tumor suppressor pathways including p53, Rb/INK4/ARF, and Notch in disease pathogenesis. […] Given the paucity of driver oncogenes in HNSCC, targeting these pathways therapeutically represents a substantial and critical challenge for improving outcomes of this disease. […] The essential role of the retinoblastoma (Rb) pathway is evidenced by the finding of inactivation of CDKN2A, encoding the cell cycle regulators p16/INK4A and p14/Arf/INK4B, in HNSCC.

• #15

  https://www.jci.org/articles/view/59889

  The finding that TP53 is mutated in both leukoplakia and benign-appearing mucosa has led to a patch-field progression model of HNSCC development, in which the index squamous carcinoma develops from a field of genetically abnormal mucosa. […] The PI3K signaling pathway is commonly activated in HNSCC, as evidenced by recurrent alterations of two central regulators: PTEN, encoding a negative regulator, and PIK3CA, encoding a positive regulator of this pathway. […] Activating mutations in two hot spot regions of the PIK3CA gene occur in 6%-11% of HNSCCs, with a potential enrichment in tumors originating from the pharynx. […] New insight into potential mechanisms of HNSCC invasion and metastasis was provided by the identification of mutations in the FAT1 gene in nine HNSCC samples in one of the two exome sequencing studies. […] The convergence of many HNSCC cancer genes on the activity of the G1 cyclin-dependent kinases suggests that targeting these kinases could have potent efficacy.

• #16 The Molecular Pathogenesis of Head and Neck Cancer | Clinical Gate

  https://clinicalgate.com/the-molecular-pathogenesis-of-head-and-neck-cancer/

  In HNSCC, EGFR expression levels are nearly ubiquitously elevated in tumor and tumor-adjacent tissue compared to corresponding normal mucosa. […] Higher expression levels and copy number gain correlate with decreased survival but have not been highly indicative of improved response to EGFR-directed therapy. […] The prevalence of the EGFRvIII variant remains controversial in HNSCC, with various studies reporting its expression to be present in anywhere from 0% to 42% of the tumors assayed. […] Another genetic alteration, reported in some cases of HNSCC, that is believed to contribute to anti-EGFR therapy resistance is mutation or amplification of the MET gene, which codes for another RTK. […] The TGF pathway has been implicated in HNSCC most commonly through 18q deletion, which contains SMAD2, SMAD3, SMAD4, and the TGFBRII gene.

• #17

  https://www.jci.org/articles/view/59889

  The finding that TP53 is mutated in both leukoplakia and benign-appearing mucosa has led to a patch-field progression model of HNSCC development, in which the index squamous carcinoma develops from a field of genetically abnormal mucosa. […] The PI3K signaling pathway is commonly activated in HNSCC, as evidenced by recurrent alterations of two central regulators: PTEN, encoding a negative regulator, and PIK3CA, encoding a positive regulator of this pathway. […] Activating mutations in two hot spot regions of the PIK3CA gene occur in 6%-11% of HNSCCs, with a potential enrichment in tumors originating from the pharynx. […] New insight into potential mechanisms of HNSCC invasion and metastasis was provided by the identification of mutations in the FAT1 gene in nine HNSCC samples in one of the two exome sequencing studies. […] The convergence of many HNSCC cancer genes on the activity of the G1 cyclin-dependent kinases suggests that targeting these kinases could have potent efficacy.

• #18 Molecular landscape of head and neck cancer and implications for therapy

  https://atm.amegroups.org/article/view/60770/html

  Understanding the mutational, genomic and transcriptomic landscape of HNSCC has leveraged better therapeutic approaches to manage this group of diseases, and it is hoped that additional insight into the molecular subtypes of HNSCC and its specific subsites will further drive improved strategies to stratify and treat patients with this debilitating disease. […] The heterogeneity of this cancer suggests a critical role for genetic alterations contributing to its carcinogenesis. […] The p53 and RB pathways are frequently abrogated in HPV-negative HNSCC, but appear to remain active in CNA-silent tumours, with mutations in HRAS and CASP8. The etiology of this subgroup of tumours remains unclear, but ageing is thought to be a risk factor. Smoking is a key etiological risk factor for HPV-negative CNA-high tumours, with many cancer genes (FAT1, NOTCH1) and pathways (WNT–catenin) being involved in their progression. […] HPV-positive tumours lack mutations and alterations in TP53 and CDKN2A in contrast with their HPV-negative counterparts.

• #19 Head and neck cancer: pathogenesis and targeted therapy

  https://pmc.ncbi.nlm.nih.gov/articles/PMC11338281/

  The pathogenesis of HNC is extremely complex, involving many aspects, including signaling pathway abnormalities, tumor microenvironment (TME) inhibition, genomic changes, epigenetic changes, and so on. Additionally, risk factors like HPV infection, smoking, alcohol abuse and poor oral health play significant roles in the onset and progression of HNC. […] HPV infection is a major factor contributing to the rising incidence of HNC patients. Among all the chronic HPV infections in HNC patients, nearly 85% are caused by HPV16 or HPV18. HPV can cause changes in oncogenes, including amplification, rearrangement, deletion, and translocation, and it induces the expansion and expression of E5/E6/E7 proteins, leading to the initiation and progression of HNC. […] E6 and E7 proteins are particularly crucial in HPV-positive HNC. E6 interacts with the retinoblastoma protein (RB), reducing inhibition of E2F transcription factors, and degrades the tumor suppressor protein p53 through a ubiquitin-dependent pathway.

• #20 Head & Neck Cancers | OncologyPRO

  https://oncologypro.esmo.org/education-library/esmo-books/essentials-for-clinicians/head-neck-cancers/pathogenesis

  HPV infection carcinogenesis: The integration of HPV DNA into the host genome disrupts the expression of factor E2, the transcriptional repressor of E6 and E7 viral proteins. […] E6 and E7 encode oncoproteins that bind and degrade p53 and retinoblastoma (Rb) tumour suppressors, respectively. Degradation of Rb induces expression of p16INK4A. […] Rb is a negative regulator of p16 protein; low Rb levels lead to p16 upregulation. HPV+ OPC is typically p53 and Rb1 wild-type and demonstrates high p16 protein levels.

• #21 Head and neck cancer – Wikipedia

  https://en.wikipedia.org/wiki/Head_and_neck_cancer

  The majority of head and neck cancer is caused by the use of alcohol or tobacco (including smokeless tobacco). An increasing number of cases are caused by the human papillomavirus (HPV). […] The way in which alcohol contributes to cancer development is not fully understood. It is thought to be related to permanent damage of DNA strands by a metabolite of alcohol called acetaldehyde. Other suggested mechanisms include nutritional deficiencies and genetic variations. […] HPV can induce tumors by several mechanisms: E6 and E7 oncogenic proteins, disruption of tumor suppressor genes, high-level DNA amplifications, generating alternative nonfunctional transcripts, interchromosomal rearrangements, and distinct host genome methylation and expression patterns, produced even when the virus is not integrated into the host genome.

• #22 Pathogenetic Action of Viruses in Head and Neck Cancer | IntechOpen

  https://www.intechopen.com/online-first/1200317

  The early oncogenes E6 and E7, for instance, are overexpressed when HPV DNA is incorporated into host cells, inactivating the tumor suppressor proteins p53 and Rb, respectively. […] About 70% of oropharyngeal malignancies (OPCs) in the US are caused by HPV, and the incidence of HPV-associated HNCs, particularly oropharyngeal squamous cell carcinoma (OPSCC), is rising sharply. […] Different HNC subtypes have distinct molecular fingerprints and viral profiles that indicate different biological activities and treatment responses. Understanding how oncogenic viruses and host factors interact is essential for creating tailored treatment plans that effectively stop the progression of HNC while lowering treatment-associated morbidity. […] The mechanisms by which oncogenic viruses induce oncogenic transformation vary, but all have important common features. For example, a virus particle is capable of bringing about transformation. All or part of the viral genome remains in the transformed cells and this genome is expressed in these cells. Transformation is a result of the degeneration of normal cellular growth signals.

• #23 ETIOPATHOGENESIS OF HEAD AND NECK CANCER.pptx

  https://www.slideshare.net/slideshow/etiopathogenesis-of-head-and-neck-cancerpptx/255463171

  Mechanism Local effects Solvent for potential carcinogens Mucosal injuryaids carcinogen uptake Acetaldehyde production by oral bacteria Chronic alcoholics -poor salivary flow -gastro oesophageal reflux. […] Viral Carcinogenesis Human Papilloma Virus Double-stranded DNA virus Papavoviridae family Replicates within epithelial cells of the hosts mucosa and skin Sexually transmitted. […] Mechanism of Carcinogenesis E2 serves as a transcriptional repressor, loss of E2 expression (typically through integration of the viral episome into the host cell DNA) results in the upregulation of early gene expression E6 protein of high-risk HPV types– destruction of p53 E7 interacts with Rb — LXCXE motif — blocking the ability of pRB to trigger cell cycle arrest. […] Development of oral cancer – multistep process Accumulation of genetic and epigenetic alterations Cellular dysregulation and uncontrolled growth. Hypermethylation- silencing of several tumor suppressor genes.

• #24 Head and neck cancer – Wikipedia

  https://en.wikipedia.org/wiki/Head_and_neck_cancer

  There are observed biological differences between HPV-positive and HPV-negative head and neck cancer, for example in terms of mutation patterns. In HPV-negative disease, genes frequently mutated include TP53, CDKN2A and PIK3CA. In HPV-positive disease, these genes are less frequently mutated, and the tumour suppressor gene p53 and pRb (protein retinoblastoma) are commonly inactivated by HPV oncoproteins E6 and E7 respectively. […] E6 sequesters p53 to promote p53 degradation, while E7 inhibits pRb. Degradation of p53 results in cells being unable to respond to checkpoint signals that are normally present to activate apoptosis when DNA damage is signalled. Loss of pRb leads to deregulation of cell proliferation and apoptosis. Both mechanisms therefore leave cell proliferation unchecked and increase the chance of carcinogenesis.

• #25 Pathogenetic Action of Viruses in Head and Neck Cancer | IntechOpen

  https://www.intechopen.com/chapters/1200317

  The impacts of virally mediated epigenetic changes on cancer pathology are: (1) epithelial-to-mesenchymal transition, (2) escape from apoptosis, (3) altered cellular metabolism, (4) angiogenesis, (5) inflammation and (6) generation of genomic instability. […] The intricate viral environment in HNC is essential to the development and spread of the malignancy. Carcinogenesis is caused by interactions between viruses and other genetic and environmental variables as well as by a lengthy latency period. Viruses can evade immune monitoring, interfere with regular cell cycle regulation and integrate into the hosts DNA. These processes lead to malignant transformation and tumor growth when paired with exposure to toxins and genetic predispositions.

• #26 Head and neck cancer – Wikipedia

  https://en.wikipedia.org/wiki/Head_and_neck_cancer

  There are observed biological differences between HPV-positive and HPV-negative head and neck cancer, for example in terms of mutation patterns. In HPV-negative disease, genes frequently mutated include TP53, CDKN2A and PIK3CA. In HPV-positive disease, these genes are less frequently mutated, and the tumour suppressor gene p53 and pRb (protein retinoblastoma) are commonly inactivated by HPV oncoproteins E6 and E7 respectively. […] E6 sequesters p53 to promote p53 degradation, while E7 inhibits pRb. Degradation of p53 results in cells being unable to respond to checkpoint signals that are normally present to activate apoptosis when DNA damage is signalled. Loss of pRb leads to deregulation of cell proliferation and apoptosis. Both mechanisms therefore leave cell proliferation unchecked and increase the chance of carcinogenesis.

• #27 The Molecular Pathogenesis of Head and Neck Cancer | Clinical Gate

  https://clinicalgate.com/the-molecular-pathogenesis-of-head-and-neck-cancer/

  The Field Cancerization Theory is defined as the presence of one or more mucosal areas consisting of epithelial cells with cancer-associated genetic or epigenetic alterations. […] Additional genetic changes are needed to transform a field into a carcinoma. […] Studies attempting to identify specific genetic characteristics that determine the risk of a field developing into cancer have shown that genetic changes at chromosome 9p, decreased cytokeratin 4 expression, and decreased cornulin expression are potential biomarkers. […] Mutation of TP53 is the earliest and most frequent mutation event observed in HPV-negative HNSCC. […] In a large portion of HNSCC without somatic TP53 mutations, the activity of p53 is compromised by other mechanisms, including E6 expression in HPV(+) cancers, which inactivates p53, and overexpression and/or amplification of MDM2, which promotes the degradation of p53.

• #28 ETIOPATHOGENESIS OF HEAD AND NECK CANCER.pptx

  https://www.slideshare.net/slideshow/etiopathogenesis-of-head-and-neck-cancerpptx/255463171

  Cancer development mutation Carcinogenesis – a multi-step process involving both the genotype and phenotype of a cell. When this process occurs at a phenotypic level, it is known as tumor progression. […] Field Cancerization First suggested by Slaughter et al in 1953 Normal epithelium from upper aero-digestive tract carcinomas was found to have altered histology. Entire regions mucosa had undergone a change related to carcinogen exposure. Explain why multiple primary and second primary tumors occur in HNSCC patients. Multiple tumors share a clonal origin and migrate to different sites – acquire distinct genetic changes. […] Loss of heterozygosity (LOH) or allelic loss at the genetic locus 9p21 appears to be the commonest genetic change, Results in the inactivation of the tumor suppressor gene p16 which encodes a cyclin-dependent kinase inhibitor (prevents cell proliferation by arresting the cell cycle in G1 stage). Another frequent mutation is LOH of the p53 gene located at 17p13.

• #29 Head & Neck Cancers | OncologyPRO

  https://oncologypro.esmo.org/education-library/esmo-books/essentials-for-clinicians/head-neck-cancers/pathogenesis

  Transformation of normal mucosa into invasive HNSCC follows a molecular progression model of multistep carcinogenesis. […] Loss of genetic material from chromosome region 9p21 and inactivation of p16 tumour suppression gene are the earliest alterations identified at transition to hyperplastic mucosa. […] Subsequent transition to dysplasia is characterised by loss of 3p and 17p and by p53 inactivation. Loss of 11q, 13q and 14q precedes transition to carcinoma in situ. […] Loss of 6p, 8p and 4q is identified during transformation to invasive HNSCC. Tobacco-related HNSCC is associated with mutation of p53 and downregulation of p16 protein. […] Leukoplakia and erythroplakia are the precursors of invasive HNSCC in the oral mucosa. […] Field carcinogenesis refers to carcinogen distribution over large areas in upper aerodigestive tracts, due to continuous exposure, rendering mucosa a potential site for cancer.

• #30

  https://journals.lww.com/md-journal/fulltext/2025/05020/differential_diagnosis_of_synchronous_double.60.aspx

  Esophageal and head and neck cancers often coexist due to field cancerization, which causes multiple squamous cell carcinomas (SCCs) in the upper aerodigestive tract. […] Multiple SCCs in the upper aerodigestive tract are explained by the concept of field cancerization, which accounts for the association of multiple tumors in this region. […] The management of the synchronous SCCs of the esophagus and head and neck is not well established, and the prognosis of each SCC is generally poor. […] Additionally, given that SCCs of the esophagus and head and neck usually have morphologically similar histology, it is difficult to distinguish double primary SCCs or synchronous metastases from each SCC. […] Furthermore, when head and neck cancer is an occult primary SCC with only metastatic neck lymph nodes detected, it is often misdiagnosed as metastasis from esophageal SCC.

• #31 Effect of tumor microenvironment on pathogenesis of the head and neck squamous cell carcinoma: a systematic review | Molecular Cancer | Full Text

  https://molecular-cancer.biomedcentral.com/articles/10.1186/s12943-019-0983-5

  The tumor microenvironment (TME) is comprised of many different cell populations, such as cancer-associated fibroblasts and various infiltrating immune cells, and non-cell components of extracellular matrix. These crucial parts of the surrounding stroma can function as both positive and negative regulators of all hallmarks of cancer development, including evasion of apoptosis, induction of angiogenesis, deregulation of the energy metabolism, resistance to the immune detection and destruction, and activation of invasion and metastasis. […] This review represents a summary of recent studies focusing on describing these effects of microenvironment on initiation and progression of the head and neck squamous cell carcinoma, focusing on oral squamous cell carcinoma, since it is becoming clear that an investigation of differences in stromal composition of the head and neck squamous cell carcinoma microenvironment and their impact on cancer development and progression may help better understand the mechanisms behind different responses to therapy and help define possible targets for clinical intervention.

• #32 Effect of tumor microenvironment on pathogenesis of the head and neck squamous cell carcinoma: a systematic review | Molecular Cancer | Full Text

  https://molecular-cancer.biomedcentral.com/articles/10.1186/s12943-019-0983-5

  The most important prognostic determinant of HNSCC tumors is considered the presence of lymph node metastases, since lymphatic metastatic spread correlates with a significant decrease in the survival rate of patients. […] While primary risk factors are tobacco use and alcohol consumption, the role of the oncogenic human papillomaviruses (HPVs) has been implicated in HNSCC as well and many studies have suggested HPV infection as a risk factor of the HNSCC development. […] The infiltration of TAMs is a major contributor to the inflammation in HNSCC and is associated with poor prognosis, lymph node metastasis and low survival. […] The growth of primary tumor is associated with the presence of immune cells, which cause inflammation frequently observed in HNSCC. […] Several studies investigated the significance of the overall population of tumor-infiltrating lymphocytes (TILs) as a prognostic marker of HNSCC.

• #33 Effect of tumor microenvironment on pathogenesis of the head and neck squamous cell carcinoma: a systematic review | Molecular Cancer | Full Text

  https://molecular-cancer.biomedcentral.com/articles/10.1186/s12943-019-0983-5

  The infiltration of TAMs is a major contributor to the inflammation in HNSCC and is associated with poor prognosis, lymph node metastasis and low survival. […] Immunohistochemical analyses of primary OSCC report higher density of CAFs in over 60% cases, while healthy tissues and adjacent stroma of premalignant lesions show no staining. […] It has been observed that increased numbers of CAFs within the primary tumor correlate with worse prognosis of HNSCC patients. […] The major ECM proteins involved in HNSCC development and progression are collagen, laminin and fibronectin. […] The expression of secreted MMP-1, MMP-2, MMP-9 and transmembrane protease membrane type 1 MMP are commonly associated with HNSCC progression. […] The activity of MMPs is regulated by tissue inhibitors of metalloproteases (TIMPs), secreted mainly by fibroblasts in the stroma.

• #34 Effect of tumor microenvironment on pathogenesis of the head and neck squamous cell carcinoma: a systematic review | Molecular Cancer | Full Text

  https://molecular-cancer.biomedcentral.com/articles/10.1186/s12943-019-0983-5

  The most important prognostic determinant of HNSCC tumors is considered the presence of lymph node metastases, since lymphatic metastatic spread correlates with a significant decrease in the survival rate of patients. […] While primary risk factors are tobacco use and alcohol consumption, the role of the oncogenic human papillomaviruses (HPVs) has been implicated in HNSCC as well and many studies have suggested HPV infection as a risk factor of the HNSCC development. […] The infiltration of TAMs is a major contributor to the inflammation in HNSCC and is associated with poor prognosis, lymph node metastasis and low survival. […] The growth of primary tumor is associated with the presence of immune cells, which cause inflammation frequently observed in HNSCC. […] Several studies investigated the significance of the overall population of tumor-infiltrating lymphocytes (TILs) as a prognostic marker of HNSCC.

• #35

  https://grantome.com/grant/NIH/R01-DE027329-01

  It is crucial to better understand immune evasion mechanisms in head and neck cancers in order to enhance their susceptibility to immunotherapy. About 90% of head and neck cancers are squamous cell carcinomas (HNSCC). Recurrent or metastatic HNSCCs are being treated with checkpoint blockade immunotherapy targeting programmed death 1 (PD-1), a co-inhibitory receptor on T cells. However, only a subset of HNSCC patients responded to such anti-PD-1 therapy (10-20%). Thus, there is an urgent need to elucidate mechanisms underlying therapy unresponsiveness to single blockade of PD-1. […] HNSCC development often associates with oncogenic mutations, such as heterozygous loss of Smad4, gain-of-function mutations of PIK3CA or loss-of-function mutations of Notch1. It remains largely unknown how HNSCCs evade immune recognition. To address this question, we performed studies with a transplanted SCC model caused by combining KrasG12D mutation and Smad4 loss (termed KRS-SCC). We found that KRS-SCC tumors completely escaped T cell-mediated anti-tumor responses, manifested with exhausted CD8 and CD4 TILs co-expressing PD-1 and LAG-3. Consistently, dual inhibition of PD-1 and LAG-3 suppressed the growth of KRS-SCCs. We propose to employ our unique mouse models and human patient samples to further elucidate immune evasion mechanisms of HNSCCs. Our proposed studies may substantially advance our understanding in mechanisms that underlie therapy failure of single PD-1 blockade.

• #36 Medical Science Monitor | Dual role of VEGF family members in the pathogenesis of head and neck cancer(HNSCC): possible link between angiogenesis and immune tolerance. – Article abstract #201014

  https://medscimonit.com/abstract/index/idArt/201014

  Dual role of VEGF family members in the pathogenesis of head and neck cancer(HNSCC): possible link between angiogenesis and immune tolerance. […] Some of the angiogenic factors released by tumor and stroma cells, including vascular endothelial growth factor (VEGF), are thought to affect DC function. […] Increased expression of VEGF-A and VEGF-C was found in tumor tissues compared to normal epithelium (P=0.001). […] However, VEGF-D levels were decreased in patients with cervical nodal metastasis as compared to patients with negative lymph node status. […] Multivariate analysis demonstrated that VEGF-A correlated with microvessel density (P=0.01), disease progression (P=0.038), a reduced number of local and peripheral mature dendritic cells (DC) (P=0.015) and an increased number of peripheral immature DCs (P=0.05). […] Taken together, our results identify VEGF-A as a multifunctional factor involved in angiogenesis, tumor progression, immunosuppression and immune tolerance.

• #37 Effect of tumor microenvironment on pathogenesis of the head and neck squamous cell carcinoma: a systematic review | Molecular Cancer | Full Text

  https://molecular-cancer.biomedcentral.com/articles/10.1186/s12943-019-0983-5

  The infiltration of TAMs is a major contributor to the inflammation in HNSCC and is associated with poor prognosis, lymph node metastasis and low survival. […] Immunohistochemical analyses of primary OSCC report higher density of CAFs in over 60% cases, while healthy tissues and adjacent stroma of premalignant lesions show no staining. […] It has been observed that increased numbers of CAFs within the primary tumor correlate with worse prognosis of HNSCC patients. […] The major ECM proteins involved in HNSCC development and progression are collagen, laminin and fibronectin. […] The expression of secreted MMP-1, MMP-2, MMP-9 and transmembrane protease membrane type 1 MMP are commonly associated with HNSCC progression. […] The activity of MMPs is regulated by tissue inhibitors of metalloproteases (TIMPs), secreted mainly by fibroblasts in the stroma.

• #38 Effect of tumor microenvironment on pathogenesis of the head and neck squamous cell carcinoma: a systematic review | Molecular Cancer | Full Text

  https://molecular-cancer.biomedcentral.com/articles/10.1186/s12943-019-0983-5

  The infiltration of TAMs is a major contributor to the inflammation in HNSCC and is associated with poor prognosis, lymph node metastasis and low survival. […] Immunohistochemical analyses of primary OSCC report higher density of CAFs in over 60% cases, while healthy tissues and adjacent stroma of premalignant lesions show no staining. […] It has been observed that increased numbers of CAFs within the primary tumor correlate with worse prognosis of HNSCC patients. […] The major ECM proteins involved in HNSCC development and progression are collagen, laminin and fibronectin. […] The expression of secreted MMP-1, MMP-2, MMP-9 and transmembrane protease membrane type 1 MMP are commonly associated with HNSCC progression. […] The activity of MMPs is regulated by tissue inhibitors of metalloproteases (TIMPs), secreted mainly by fibroblasts in the stroma.

• #39 Effect of tumor microenvironment on pathogenesis of the head and neck squamous cell carcinoma: a systematic review | Molecular Cancer | Full Text

  https://molecular-cancer.biomedcentral.com/articles/10.1186/s12943-019-0983-5

  The infiltration of TAMs is a major contributor to the inflammation in HNSCC and is associated with poor prognosis, lymph node metastasis and low survival. […] Immunohistochemical analyses of primary OSCC report higher density of CAFs in over 60% cases, while healthy tissues and adjacent stroma of premalignant lesions show no staining. […] It has been observed that increased numbers of CAFs within the primary tumor correlate with worse prognosis of HNSCC patients. […] The major ECM proteins involved in HNSCC development and progression are collagen, laminin and fibronectin. […] The expression of secreted MMP-1, MMP-2, MMP-9 and transmembrane protease membrane type 1 MMP are commonly associated with HNSCC progression. […] The activity of MMPs is regulated by tissue inhibitors of metalloproteases (TIMPs), secreted mainly by fibroblasts in the stroma.

• #40 Effect of tumor microenvironment on pathogenesis of the head and neck squamous cell carcinoma: a systematic review | Molecular Cancer | Full Text

  https://molecular-cancer.biomedcentral.com/articles/10.1186/s12943-019-0983-5

  The loss of E-cadherin and high vimentin levels have been associated with tumor progression and an increase of metastases in HNSCC patients. […] The expression of MMPs commonly overexpressed in HNSCC include MMP-1, MMP-2, MMP-3, MMP-7, MMP-8, MMP-9, MMP-10, MMP-11, MMP-13, and MT1-MMP. […] The expression of secreted MMP-1, MMP-2, MMP-9 and transmembrane protease membrane type 1 MMP are commonly associated with HNSCC progression. […] The expression of MMP-2 and MMP-9 levels have been reported in correlation with local invasion, cervical nodal metastasis, tumor progression and prognosis of HNSCC patients. […] The role of CAFs in the process of EMT in many types of cancer, including HNSCC, has been intensely researched. […] The presence of CAFs promotes cancer cell invasion. […] The stimulating effect of CAFs on HNSCC invasion has been described by various in vitro assays.

• #41 Effect of tumor microenvironment on pathogenesis of the head and neck squamous cell carcinoma: a systematic review | Molecular Cancer | Full Text

  https://molecular-cancer.biomedcentral.com/articles/10.1186/s12943-019-0983-5

  The possible contribution of CAFs to the EMT induction in HNSCC carcinoma cells has been implicated by immunohistochemical analyses, in which markers associated with EMT in CAFs in paired primary and metastatic OSCC showed that Ki-67+ metastatic carcinoma cells downregulate E-cadherin when in direct contact with CAFs. […] It has been reported that expressions of EMT promoters, Snail, Slug, TWIST and SMAD nuclear interacting protein-1(SNIP1), which are regulated by HIF-1, correlate with induction of EMT phenotype in OSCC cells in vitro. […] A study by Huang et al. reported that SLUG regulated the expression of MT4-MMP under hypoxia, which promoted the invasiveness of HNSCC cell lines. […] It has been suggested that hypoxia induces EMT in OSCC via activation of the Notch signaling pathway and the inhibition of the Notch signaling pathway suppresses EMT.

• #42 Effect of tumor microenvironment on pathogenesis of the head and neck squamous cell carcinoma: a systematic review | Molecular Cancer | Full Text

  https://molecular-cancer.biomedcentral.com/articles/10.1186/s12943-019-0983-5

  The infiltration of TAMs is a major contributor to the inflammation in HNSCC and is associated with poor prognosis, lymph node metastasis and low survival. […] Immunohistochemical analyses of primary OSCC report higher density of CAFs in over 60% cases, while healthy tissues and adjacent stroma of premalignant lesions show no staining. […] It has been observed that increased numbers of CAFs within the primary tumor correlate with worse prognosis of HNSCC patients. […] The major ECM proteins involved in HNSCC development and progression are collagen, laminin and fibronectin. […] The expression of secreted MMP-1, MMP-2, MMP-9 and transmembrane protease membrane type 1 MMP are commonly associated with HNSCC progression. […] The activity of MMPs is regulated by tissue inhibitors of metalloproteases (TIMPs), secreted mainly by fibroblasts in the stroma.

• #43 Effect of tumor microenvironment on pathogenesis of the head and neck squamous cell carcinoma: a systematic review | Molecular Cancer | Full Text

  https://molecular-cancer.biomedcentral.com/articles/10.1186/s12943-019-0983-5

  The infiltration of TAMs is a major contributor to the inflammation in HNSCC and is associated with poor prognosis, lymph node metastasis and low survival. […] Immunohistochemical analyses of primary OSCC report higher density of CAFs in over 60% cases, while healthy tissues and adjacent stroma of premalignant lesions show no staining. […] It has been observed that increased numbers of CAFs within the primary tumor correlate with worse prognosis of HNSCC patients. […] The major ECM proteins involved in HNSCC development and progression are collagen, laminin and fibronectin. […] The expression of secreted MMP-1, MMP-2, MMP-9 and transmembrane protease membrane type 1 MMP are commonly associated with HNSCC progression. […] The activity of MMPs is regulated by tissue inhibitors of metalloproteases (TIMPs), secreted mainly by fibroblasts in the stroma.

• #44 Effect of tumor microenvironment on pathogenesis of the head and neck squamous cell carcinoma: a systematic review | Molecular Cancer | Full Text

  https://molecular-cancer.biomedcentral.com/articles/10.1186/s12943-019-0983-5

  The loss of E-cadherin and high vimentin levels have been associated with tumor progression and an increase of metastases in HNSCC patients. […] The expression of MMPs commonly overexpressed in HNSCC include MMP-1, MMP-2, MMP-3, MMP-7, MMP-8, MMP-9, MMP-10, MMP-11, MMP-13, and MT1-MMP. […] The expression of secreted MMP-1, MMP-2, MMP-9 and transmembrane protease membrane type 1 MMP are commonly associated with HNSCC progression. […] The expression of MMP-2 and MMP-9 levels have been reported in correlation with local invasion, cervical nodal metastasis, tumor progression and prognosis of HNSCC patients. […] The role of CAFs in the process of EMT in many types of cancer, including HNSCC, has been intensely researched. […] The presence of CAFs promotes cancer cell invasion. […] The stimulating effect of CAFs on HNSCC invasion has been described by various in vitro assays.

• #45 Effect of tumor microenvironment on pathogenesis of the head and neck squamous cell carcinoma: a systematic review | Molecular Cancer | Full Text

  https://molecular-cancer.biomedcentral.com/articles/10.1186/s12943-019-0983-5

  The possible contribution of CAFs to the EMT induction in HNSCC carcinoma cells has been implicated by immunohistochemical analyses, in which markers associated with EMT in CAFs in paired primary and metastatic OSCC showed that Ki-67+ metastatic carcinoma cells downregulate E-cadherin when in direct contact with CAFs. […] It has been reported that expressions of EMT promoters, Snail, Slug, TWIST and SMAD nuclear interacting protein-1(SNIP1), which are regulated by HIF-1, correlate with induction of EMT phenotype in OSCC cells in vitro. […] A study by Huang et al. reported that SLUG regulated the expression of MT4-MMP under hypoxia, which promoted the invasiveness of HNSCC cell lines. […] It has been suggested that hypoxia induces EMT in OSCC via activation of the Notch signaling pathway and the inhibition of the Notch signaling pathway suppresses EMT.

• #46 The Molecular Pathogenesis of Head and Neck Cancer | Clinical Gate

  https://clinicalgate.com/the-molecular-pathogenesis-of-head-and-neck-cancer/

  The loss of SMAD4 expression in these animals correlated with increased expression of TGFBRI and increased activation of SMAD3, and the Fanconi anemia DNA repair pathway was found to be downregulated. […] The exact mechanism(s) of their interaction, as well as their independent and/or cooperative contributions to invasion and metastasis in HNSCC, still need to be precisely elucidated. […] The exploitation of neo-angiogenesis, usually by producing angiogenic factors, is common to all solid tumors. […] Many studies have linked VEGF expression to HNSCC prognosis, including a meta-analysis that found a significantly increased risk of 1.88, as well as an association with VEGF expression and metastasis to lymph nodes. […] Though functional studies have not yet been performed, these mutations may underlie a mechanism permitting the dissociation of cells from an otherwise cohesive sheet of cancerous epithelium, ultimately allowing for migration and metastasis of HNSCC tumors.

• #47 Effect of tumor microenvironment on pathogenesis of the head and neck squamous cell carcinoma: a systematic review | Molecular Cancer | Full Text

  https://molecular-cancer.biomedcentral.com/articles/10.1186/s12943-019-0983-5

  The possible contribution of CAFs to the EMT induction in HNSCC carcinoma cells has been implicated by immunohistochemical analyses, in which markers associated with EMT in CAFs in paired primary and metastatic OSCC showed that Ki-67+ metastatic carcinoma cells downregulate E-cadherin when in direct contact with CAFs. […] It has been reported that expressions of EMT promoters, Snail, Slug, TWIST and SMAD nuclear interacting protein-1(SNIP1), which are regulated by HIF-1, correlate with induction of EMT phenotype in OSCC cells in vitro. […] A study by Huang et al. reported that SLUG regulated the expression of MT4-MMP under hypoxia, which promoted the invasiveness of HNSCC cell lines. […] It has been suggested that hypoxia induces EMT in OSCC via activation of the Notch signaling pathway and the inhibition of the Notch signaling pathway suppresses EMT.

• #48 Effect of tumor microenvironment on pathogenesis of the head and neck squamous cell carcinoma: a systematic review | Molecular Cancer | Full Text

  https://molecular-cancer.biomedcentral.com/articles/10.1186/s12943-019-0983-5

  The results also implicate that the invasive phenotype of cancer cells is regulated by cell contact-dependent hypoxia-mediated Notch signaling coupled with the paracrine activation of the EGFR, which is mediated by the ADAM12-dependent secretion of HB-EGF. […] The study showed that hypoxia increased the expression levels of genes associated with glycolysis, such as MCT1, MCT4, GLUT1 and LDHA in HNSCC cells and stimulated uptake of glucose, production of lactate and cell invasion in vitro. […] The mechanisms of extravasation of tumor cells have been well described in many types of cancer; however, the effect of microenvironmental factors on extravasation in HNSCC has yet to be investigated.

• #49 Effect of tumor microenvironment on pathogenesis of the head and neck squamous cell carcinoma: a systematic review | Molecular Cancer | Full Text

  https://molecular-cancer.biomedcentral.com/articles/10.1186/s12943-019-0983-5

  The results also implicate that the invasive phenotype of cancer cells is regulated by cell contact-dependent hypoxia-mediated Notch signaling coupled with the paracrine activation of the EGFR, which is mediated by the ADAM12-dependent secretion of HB-EGF. […] The study showed that hypoxia increased the expression levels of genes associated with glycolysis, such as MCT1, MCT4, GLUT1 and LDHA in HNSCC cells and stimulated uptake of glucose, production of lactate and cell invasion in vitro. […] The mechanisms of extravasation of tumor cells have been well described in many types of cancer; however, the effect of microenvironmental factors on extravasation in HNSCC has yet to be investigated.

• #50 The Molecular Pathogenesis of Head and Neck Cancer | Clinical Gate

  https://clinicalgate.com/the-molecular-pathogenesis-of-head-and-neck-cancer/

  The loss of SMAD4 expression in these animals correlated with increased expression of TGFBRI and increased activation of SMAD3, and the Fanconi anemia DNA repair pathway was found to be downregulated. […] The exact mechanism(s) of their interaction, as well as their independent and/or cooperative contributions to invasion and metastasis in HNSCC, still need to be precisely elucidated. […] The exploitation of neo-angiogenesis, usually by producing angiogenic factors, is common to all solid tumors. […] Many studies have linked VEGF expression to HNSCC prognosis, including a meta-analysis that found a significantly increased risk of 1.88, as well as an association with VEGF expression and metastasis to lymph nodes. […] Though functional studies have not yet been performed, these mutations may underlie a mechanism permitting the dissociation of cells from an otherwise cohesive sheet of cancerous epithelium, ultimately allowing for migration and metastasis of HNSCC tumors.

• #51 Cell death in head and neck cancer pathogenesis and treatment | Cell Death & Disease

  https://www.nature.com/articles/s41419-021-03474-5

  Many cancer therapies aim to trigger apoptosis in cancer cells. […] Molecular heterogeneity of head and neck squamous cell carcinomas (HNSCC) causing unpredictability of the clinical response represents a grave challenge for oncologists and seems to be a critical component of treatment response. […] How exactly cells die is very important because the predominant type of cell death can have multiple impacts on the therapeutic response as cell death itself acts as a second messenger. […] The large proportion of this clinical heterogeneity probably lies in alterations of cell death pathways. […] Specific sensitivity of cancer cells to some form of programmed cell death provides an interesting therapeutic window. […] HPV infection probably covers most of the HNSCC heterogeneity. […] The influence of HPV on triggering of different kinds of cell death in HNSCC is discussed in a lesser extent, which is unfortunate because many viruses, including HPV, have developed numerous strategies to modulate host cell death to persist in the host for a long time without being eliminated.

• #52 Cell death in head and neck cancer pathogenesis and treatment | Cell Death & Disease

  https://www.nature.com/articles/s41419-021-03474-5

  Many cancer therapies aim to trigger apoptosis in cancer cells. […] Molecular heterogeneity of head and neck squamous cell carcinomas (HNSCC) causing unpredictability of the clinical response represents a grave challenge for oncologists and seems to be a critical component of treatment response. […] How exactly cells die is very important because the predominant type of cell death can have multiple impacts on the therapeutic response as cell death itself acts as a second messenger. […] The large proportion of this clinical heterogeneity probably lies in alterations of cell death pathways. […] Specific sensitivity of cancer cells to some form of programmed cell death provides an interesting therapeutic window. […] HPV infection probably covers most of the HNSCC heterogeneity. […] The influence of HPV on triggering of different kinds of cell death in HNSCC is discussed in a lesser extent, which is unfortunate because many viruses, including HPV, have developed numerous strategies to modulate host cell death to persist in the host for a long time without being eliminated.

• #53 Cell death mechanisms in head and neck cancer cells in response to low and high-LET radiation | Expert Reviews in Molecular Medicine | Cambridge Core

  https://www.cambridge.org/core/journals/expert-reviews-in-molecular-medicine/article/cell-death-mechanisms-in-head-and-neck-cancer-cells-in-response-to-low-and-highlet-radiation/5D81C15D79DA4C3B485D4367D5C7CBD3

  Despite this, there are several mechanisms of cell death that may account for IR-induced cell killing, namely apoptosis, necrosis, mitotic catastrophe, senescence and autophagy. […] The form of cell death induced by a particular anti-cancer agent such as IR depends on several factors, including cell type, the type of DNA damage to which the cell is exposed and the dose of the agent used. […] This increase in CDD represents a challenge to the cellular DNA repair machinery and therefore can contribute to the therapeutic effect of PBT, and more so of heavy ions (such as carbon) that are of significantly higher LET. […] The long held concept that cells either repair their damage or undergo apoptosis after IR treatment is outdated, and the role of apoptosis in the tumour response to radiation has been minimised considering that most tumours actually lose the ability to initiate the apoptotic pathway.

• #54 Cell death mechanisms in head and neck cancer cells in response to low and high-LET radiation | Expert Reviews in Molecular Medicine | Cambridge Core

  https://www.cambridge.org/core/journals/expert-reviews-in-molecular-medicine/article/cell-death-mechanisms-in-head-and-neck-cancer-cells-in-response-to-low-and-highlet-radiation/5D81C15D79DA4C3B485D4367D5C7CBD3

  Head and neck squamous cell carcinoma (HNSCC) is a common malignancy that develops in or around the throat, larynx, nose, sinuses and mouth, and is mostly treated with a combination of chemo- and radiotherapy (RT). The mechanisms by which conventional photon RT achieves this have been extensively studied over several decades, but little is known about the cell death pathways that are activated in response to RT of increasing linear energy transfer (LET), including proton beam therapy and heavy ions. […] The mechanisms by which photon (X-ray) irradiation kills cancer cells have been studied in depth, but little is known in relation to PBT and other high-LET particles, including carbon ions. […] The main goal of RT is to cause sufficient damage to macromolecules particularly DNA, but also to lipids, proteins and many metabolites and therefore to promote cancer cell death while preserving the surrounding healthy tissue.

• #55 Cell death mechanisms in head and neck cancer cells in response to low and high-LET radiation | Expert Reviews in Molecular Medicine | Cambridge Core

  https://www.cambridge.org/core/journals/expert-reviews-in-molecular-medicine/article/cell-death-mechanisms-in-head-and-neck-cancer-cells-in-response-to-low-and-highlet-radiation/5D81C15D79DA4C3B485D4367D5C7CBD3

  Despite this, there are several mechanisms of cell death that may account for IR-induced cell killing, namely apoptosis, necrosis, mitotic catastrophe, senescence and autophagy. […] The form of cell death induced by a particular anti-cancer agent such as IR depends on several factors, including cell type, the type of DNA damage to which the cell is exposed and the dose of the agent used. […] This increase in CDD represents a challenge to the cellular DNA repair machinery and therefore can contribute to the therapeutic effect of PBT, and more so of heavy ions (such as carbon) that are of significantly higher LET. […] The long held concept that cells either repair their damage or undergo apoptosis after IR treatment is outdated, and the role of apoptosis in the tumour response to radiation has been minimised considering that most tumours actually lose the ability to initiate the apoptotic pathway.

• #56 Cell death mechanisms in head and neck cancer cells in response to low and high-LET radiation | Expert Reviews in Molecular Medicine | Cambridge Core

  https://www.cambridge.org/core/journals/expert-reviews-in-molecular-medicine/article/cell-death-mechanisms-in-head-and-neck-cancer-cells-in-response-to-low-and-highlet-radiation/5D81C15D79DA4C3B485D4367D5C7CBD3

  A more important role in the anti-tumour effect of radiation is played by mitotic catastrophe or senescence, although as already stated previously, both these mechanisms cannot be considered strictly cell death and therefore rely on other pathways (e.g. apoptosis or autophagy) that trigger this phenotype. […] The mechanisms of cell death in response to high-LET radiation in HNSCC cells have not been studied extensively. […] This demonstrates the differences in inherent radioresistance of the different HNSCC cells to both low and high-LET radiation. […] In summary, evidence suggests that low-LET radiation exposure may trigger different types of HNSCC cell death mechanism, and that the cells undergo a specific pathway depending on the radiation dose but also the cellular genetic profile.

• #57 Cell death in head and neck cancer pathogenesis and treatment | Cell Death & Disease

  https://www.nature.com/articles/s41419-021-03474-5

  Deep understanding of the sensitivity or resistance to a specific cell death type given by certain genetic background and/or microenvironment that occur during the HNSCC pathogenesis may reveal targets for novel therapeutic approaches. […] The predominant type of cell death can have multiple impacts on the therapeutic response as cell death acts as a second messenger that guides both immune system and tissue microenvironment to ensure tissue repair and homoeostasis. […] HPV-positive HNSCC may be more sensitive to mitochondria-targeted treatments, such as mitocans. […] The MS subgroup of HNSCC, having an elevated expression of EMT-associated genes, could be the most sensitive to ferroptosis.

• #58 Cell death in head and neck cancer pathogenesis and treatment | Cell Death & Disease

  https://www.nature.com/articles/s41419-021-03474-5

  Deep understanding of the sensitivity or resistance to a specific cell death type given by certain genetic background and/or microenvironment that occur during the HNSCC pathogenesis may reveal targets for novel therapeutic approaches. […] The predominant type of cell death can have multiple impacts on the therapeutic response as cell death acts as a second messenger that guides both immune system and tissue microenvironment to ensure tissue repair and homoeostasis. […] HPV-positive HNSCC may be more sensitive to mitochondria-targeted treatments, such as mitocans. […] The MS subgroup of HNSCC, having an elevated expression of EMT-associated genes, could be the most sensitive to ferroptosis.

• #59 Head and neck cancer: pathogenesis and targeted therapy

  https://pmc.ncbi.nlm.nih.gov/articles/PMC11338281/

  The JAK/STAT signaling pathway is abnormally activated in HNC due to mutations in various oncogenes affecting receptors, downstream mediators, and related transcription factors. […] Several studies have shown that the upregulation and abnormal activation of NFB family plays significant role in HNSCC. Among the pathogenic factors of HNSCC, cigarette smoke can lead to phosphorylation and degradation of IB, activating the NFB pathway. […] Research data have showed that HGF and MET proteins were overexpressed in HNSCC. These proteins influence the onset and progression of HNSCC through multiple pathways. […] TP53 mutations are the most frequent among the TSGs in HNSCC. The primary causes of p53 protein dysfunction in HNSCC include gene mutation and HPV infection. […] In HNC, genetic and epigenetic factors combine to influence gene expression, leading to changes in cell signaling pathways that regulate tumor growth, DNA repair, antiapoptosis, angiogenesis, resistance to external factors, and epithelial mesenchymal transformation. […] Epigenetic modifications, unlike gene mutations, alter the phenotype without changing the DNA sequence. These modifications are heritable and reversible.

• #60 Head and neck cancer: pathogenesis and targeted therapy

  https://pmc.ncbi.nlm.nih.gov/articles/PMC11338281/

  The JAK/STAT signaling pathway is abnormally activated in HNC due to mutations in various oncogenes affecting receptors, downstream mediators, and related transcription factors. […] Several studies have shown that the upregulation and abnormal activation of NFB family plays significant role in HNSCC. Among the pathogenic factors of HNSCC, cigarette smoke can lead to phosphorylation and degradation of IB, activating the NFB pathway. […] Research data have showed that HGF and MET proteins were overexpressed in HNSCC. These proteins influence the onset and progression of HNSCC through multiple pathways. […] TP53 mutations are the most frequent among the TSGs in HNSCC. The primary causes of p53 protein dysfunction in HNSCC include gene mutation and HPV infection. […] In HNC, genetic and epigenetic factors combine to influence gene expression, leading to changes in cell signaling pathways that regulate tumor growth, DNA repair, antiapoptosis, angiogenesis, resistance to external factors, and epithelial mesenchymal transformation. […] Epigenetic modifications, unlike gene mutations, alter the phenotype without changing the DNA sequence. These modifications are heritable and reversible.

• #61 ETIOPATHOGENESIS OF HEAD AND NECK CANCER.pptx

  https://www.slideshare.net/slideshow/etiopathogenesis-of-head-and-neck-cancerpptx/255463171

  Mechanism Local effects Solvent for potential carcinogens Mucosal injuryaids carcinogen uptake Acetaldehyde production by oral bacteria Chronic alcoholics -poor salivary flow -gastro oesophageal reflux. […] Viral Carcinogenesis Human Papilloma Virus Double-stranded DNA virus Papavoviridae family Replicates within epithelial cells of the hosts mucosa and skin Sexually transmitted. […] Mechanism of Carcinogenesis E2 serves as a transcriptional repressor, loss of E2 expression (typically through integration of the viral episome into the host cell DNA) results in the upregulation of early gene expression E6 protein of high-risk HPV types– destruction of p53 E7 interacts with Rb — LXCXE motif — blocking the ability of pRB to trigger cell cycle arrest. […] Development of oral cancer – multistep process Accumulation of genetic and epigenetic alterations Cellular dysregulation and uncontrolled growth. Hypermethylation- silencing of several tumor suppressor genes.

• #62 ETIOPATHOGENESIS OF HEAD AND NECK CANCER.pptx

  https://www.slideshare.net/slideshow/etiopathogenesis-of-head-and-neck-cancerpptx/255463171

  The genes found hypermethylated include – Cell cycle control genes (p16, p15), Apoptosis genes (p14, DAPK, p73 and RASSF1A), Wnt signaling genes (APC, WIF1, RUNX3), Cell-cell adhesion genes (E-cadherin), DNA-repair genes (MGMT, BRCA1 and hMLH1), Tumor suppressor genes (p16, MLH1, BRCA1 CDKN2A, pRB, APC, PTEN, BRCA1, VHL and CDH1), Metastasis-related genes, Hormone receptor genes and genes inhibiting angiogenesis.

• #63 Research progress on the role and mechanism of circular RNA in drug resistance of head and neck squamous cell carcinoma

  https://www.oaepublish.com/articles/cdr.2024.57

  Drug resistance in tumors constitutes a significant obstacle to tumor therapy. Head and neck squamous cell carcinoma (HNSCC) presents a major challenge due to its deep anatomical location, limited space, and complex structure. […] Recent advances in high-throughput sequencing and bioinformatics technology revealed that circRNAs participate in tumor proliferation, invasion, migration, and drug resistance. […] A better understanding of the association between circRNAs and HNSCC will help us to more effectively study and explore new early diagnostic indicators and therapeutic targets for HNSCC. This review aims to clarify the role of circRNAs in drug resistance in HNSCC and its potential as a diagnostic and therapeutic target. […] circRNAs are involved in this process. For example, overexpression of circ-000543 in radioinsensitive NPC contributes to the development of radioresistance. This circRNA functions by binding to miR-9, thereby upregulating platelet-derived growth factor receptor B (PDGFRB) expression.

• #64 Research progress on the role and mechanism of circular RNA in drug resistance of head and neck squamous cell carcinoma

  https://www.oaepublish.com/articles/cdr.2024.57

  The emergence of multidrug resistance in tumor cells is the main reason for chemotherapy failure. […] With the extensive investigation of circRNA biological function, increasing evidence suggests that certain circRNAs are significantly upregulated in drug-resistant HNSCC tissues. Furthermore, circRNAs are closely associated with some signaling pathways that are involved in drug resistance of HNSCC, such as PI3K/AKT, MAPK, NF-B, and Wnt/-catenin signaling pathways. […] These circRNAs can act as „sponges” for miRNAs by containing multiple miRNA binding sites, thereby adsorbing and inhibiting miRNA activity and subsequently regulating downstream pathways that affect tumor sensitivity to drugs. […] Specific circRNAs have been reported to play a role in metastasis and resistance to chemotherapy in NPC.

• #65 Pathogenetic Action of Viruses in Head and Neck Cancer | IntechOpen

  https://www.intechopen.com/chapters/1200317

  Studies of the oncogenic activity of proteins encoded by oncogenic viruses, especially DNA viruses, have greatly contributed to elucidating the role of retinoblastoma (Rb) proteins and the repressor gene p53 as regulators of cell growth. […] The tumor suppressor gene TP53 is located on chromosome 17p13 and encodes the nuclear protein p53 (transcription factor), which is involved in maintaining the integrity of the genome and is responsible for the smooth functioning of repair mechanisms in case of DNA damage. […] The ability to understand mutation in relation to viral infection provides an additional physiological dimension to the evolution of viral replication and the strategy by which one can examine mutation. […] Oncogenic viruses contribute to carcinogenesis by altering host epigenomes and using host epigenetic machinery.

• #66 Pathogenetic Action of Viruses in Head and Neck Cancer | IntechOpen

  https://www.intechopen.com/online-first/1200317

  The impacts of virally mediated epigenetic changes on cancer pathology are: (1) epithelial-to-mesenchymal transition, (2) escape from apoptosis, (3) altered cellular metabolism, (4) angiogenesis, (5) inflammation and (6) generation of genomic instability. […] EBV is classified as a Group I carcinogen by IARC. […] EBV adopts a hit and run tactic, manipulating host epigenetic procedures to start an oncogenic pathway even after the virus has been eliminated. […] Latent viral proteins, including EBV nuclear antigen (EBNA) and latent membrane proteins (LMPs), which disrupt cell function, promote proliferation and halt apoptosis, are responsible for the carcinogenic consequences of EBV. […] HHV-8 exerts its oncogenic effects through viral proteins that establish latent infection in endothelial cells, disrupt cellular control mechanisms and promote uncontrolled cell proliferation and survival. […] The carcinogenic potential of viruses in the head and neck region can be impacted by co-infections with other pathogens, which can exacerbate the progression of cancer through a variety of mechanisms.

• #67 Molecular mechanism(s) of regulation(s) of c-MET/HGF signaling in head and neck cancer | Molecular Cancer | Full Text

  https://molecular-cancer.biomedcentral.com/articles/10.1186/s12943-022-01503-1

  c-MET pathway has been reported to be associated with several other signaling pathways in HNSCC. […] c-MET signaling is also known to contribute widely in metabolic reprogramming of tumor cells. […] The c-MET/HGF signaling is also known to contribute widely in metabolic reprogramming of tumor cells. Increased glucose metabolism is highly preferred by cancer cells to yield much higher ATP and it also generates biosynthesis relevant precursor molecules. […] Chemoresistance towards EGFR inhibition by small molecule tyrosine kinase inhibitors such as gefitinib or erlotinib are common features in clinical trials. Upregulation of c-MET has also reported its contribution towards cetuximab resistance in HNSCC patients. […] c-MET has a major contribution towards compensating for inhibition of RTK pathways that help in proliferation and metastasis in HNSCC. Therefore, targeting c-MET along with other receptor tyrosine kinases can bring effective therapeutic strategies.

• #68 Molecular mechanism(s) of regulation(s) of c-MET/HGF signaling in head and neck cancer | Molecular Cancer | Full Text

  https://molecular-cancer.biomedcentral.com/articles/10.1186/s12943-022-01503-1

  c-MET pathway has been reported to be associated with several other signaling pathways in HNSCC. […] c-MET signaling is also known to contribute widely in metabolic reprogramming of tumor cells. […] The c-MET/HGF signaling is also known to contribute widely in metabolic reprogramming of tumor cells. Increased glucose metabolism is highly preferred by cancer cells to yield much higher ATP and it also generates biosynthesis relevant precursor molecules. […] Chemoresistance towards EGFR inhibition by small molecule tyrosine kinase inhibitors such as gefitinib or erlotinib are common features in clinical trials. Upregulation of c-MET has also reported its contribution towards cetuximab resistance in HNSCC patients. […] c-MET has a major contribution towards compensating for inhibition of RTK pathways that help in proliferation and metastasis in HNSCC. Therefore, targeting c-MET along with other receptor tyrosine kinases can bring effective therapeutic strategies.

• #69 Molecular mechanism(s) of regulation(s) of c-MET/HGF signaling in head and neck cancer | Molecular Cancer | Full Text

  https://molecular-cancer.biomedcentral.com/articles/10.1186/s12943-022-01503-1

  c-MET pathway has been reported to be associated with several other signaling pathways in HNSCC. […] c-MET signaling is also known to contribute widely in metabolic reprogramming of tumor cells. […] The c-MET/HGF signaling is also known to contribute widely in metabolic reprogramming of tumor cells. Increased glucose metabolism is highly preferred by cancer cells to yield much higher ATP and it also generates biosynthesis relevant precursor molecules. […] Chemoresistance towards EGFR inhibition by small molecule tyrosine kinase inhibitors such as gefitinib or erlotinib are common features in clinical trials. Upregulation of c-MET has also reported its contribution towards cetuximab resistance in HNSCC patients. […] c-MET has a major contribution towards compensating for inhibition of RTK pathways that help in proliferation and metastasis in HNSCC. Therefore, targeting c-MET along with other receptor tyrosine kinases can bring effective therapeutic strategies.

• #70 Effect of tumor microenvironment on pathogenesis of the head and neck squamous cell carcinoma: a systematic review | Molecular Cancer | Full Text

  https://molecular-cancer.biomedcentral.com/articles/10.1186/s12943-019-0983-5

  The results also implicate that the invasive phenotype of cancer cells is regulated by cell contact-dependent hypoxia-mediated Notch signaling coupled with the paracrine activation of the EGFR, which is mediated by the ADAM12-dependent secretion of HB-EGF. […] The study showed that hypoxia increased the expression levels of genes associated with glycolysis, such as MCT1, MCT4, GLUT1 and LDHA in HNSCC cells and stimulated uptake of glucose, production of lactate and cell invasion in vitro. […] The mechanisms of extravasation of tumor cells have been well described in many types of cancer; however, the effect of microenvironmental factors on extravasation in HNSCC has yet to be investigated.

• #71 Role of Glutathione in Head and Neck Cancer Pathogenesis: Khan, Sami Ullah: 9786202511957: Amazon.com: Books

  https://www.amazon.com/Role-Glutathione-Head-Cancer-Pathogenesis/dp/6202511958

  This book is about the glutathione which is an important thiol compound that plays an important role in the antioxidant defense system required for the maintenance of redox status of the cell, defense against free oxygen radicals (ROS) and detoxification of toxic compounds. […] In the present study, we investigated the alterations of the glutathione levels in blood and tissue samples from patients with head and neck cancer. […] The results indicated that glutathione levels total and reduced, in the blood of head and neck cancer patients were significantly lowered as compared to respective controls. […] In contrast, the levels of glutathione total and glutathione reduced were significantly increased in tissues of patients with head and neck cancer compared to the tissues adjacent to cancer-free tissues used as controls.

• #72 Role of Glutathione in Head and Neck Cancer Pathogenesis: Khan, Sami Ullah: 9786202511957: Amazon.com: Books

  https://www.amazon.com/Role-Glutathione-Head-Cancer-Pathogenesis/dp/6202511958

  These changes in glutathione levels in blood and tumors of head and cancer may be due to increased utilization of glutathione due to variant genotypes and reactive oxygen species (ROS). […] We concluded that the glutathione levels in head and neck cancer patient’s blood or tissues may act as a prognostic marker of head and neck cancer, thus deserves further investigations.

• #73 Oral Microbiota—A New Frontier in the Pathogenesis and Management of Head and Neck Cancers

  https://helda.helsinki.fi/items/b3a46736-a5ee-4945-86fa-8b109ee8660e

  Head and neck squamous cell carcinoma (HNSCC) is a group of common and aggressive tumors. […] Recent evidence suggests that oral microbiota is associated with carcinogenesis. […] Importantly, many oral pathogens, such as Porphyromonas gingivalis and Fusobacterium nucleatum were linked to certain oral potentially malignant lesions and various types of HNSCC. […] Furthermore, we summarized the association between the expression profiles of different oral bacterial species and their tumorigenic and prognostic effects in cancer patients. […] We also discussed the current limitations of this newly emerging area and the potential microbiota-related strategies for preventing and treating HNSCC. […] Whilst many clinical studies are underway to unravel the role of oral microbiota in cancer, the limited available data and experimental approaches reflect the newness of this promising yet challenging field.

• #74 Oral Microbiota—A New Frontier in the Pathogenesis and Management of Head and Neck Cancers

  https://helda.helsinki.fi/items/b3a46736-a5ee-4945-86fa-8b109ee8660e

  Head and neck squamous cell carcinoma (HNSCC) is a group of common and aggressive tumors. […] Recent evidence suggests that oral microbiota is associated with carcinogenesis. […] Importantly, many oral pathogens, such as Porphyromonas gingivalis and Fusobacterium nucleatum were linked to certain oral potentially malignant lesions and various types of HNSCC. […] Furthermore, we summarized the association between the expression profiles of different oral bacterial species and their tumorigenic and prognostic effects in cancer patients. […] We also discussed the current limitations of this newly emerging area and the potential microbiota-related strategies for preventing and treating HNSCC. […] Whilst many clinical studies are underway to unravel the role of oral microbiota in cancer, the limited available data and experimental approaches reflect the newness of this promising yet challenging field.

• #75 ETIOPATHOGENESIS OF HEAD AND NECK CANCER.pptx

  https://www.slideshare.net/slideshow/etiopathogenesis-of-head-and-neck-cancerpptx/255463171

  Mechanism Local effects Solvent for potential carcinogens Mucosal injuryaids carcinogen uptake Acetaldehyde production by oral bacteria Chronic alcoholics -poor salivary flow -gastro oesophageal reflux. […] Viral Carcinogenesis Human Papilloma Virus Double-stranded DNA virus Papavoviridae family Replicates within epithelial cells of the hosts mucosa and skin Sexually transmitted. […] Mechanism of Carcinogenesis E2 serves as a transcriptional repressor, loss of E2 expression (typically through integration of the viral episome into the host cell DNA) results in the upregulation of early gene expression E6 protein of high-risk HPV types– destruction of p53 E7 interacts with Rb — LXCXE motif — blocking the ability of pRB to trigger cell cycle arrest. […] Development of oral cancer – multistep process Accumulation of genetic and epigenetic alterations Cellular dysregulation and uncontrolled growth. Hypermethylation- silencing of several tumor suppressor genes.

• #76 Effect of tumor microenvironment on pathogenesis of the head and neck squamous cell carcinoma: a systematic review | Molecular Cancer | Full Text

  https://molecular-cancer.biomedcentral.com/articles/10.1186/s12943-019-0983-5

  The most important prognostic determinant of HNSCC tumors is considered the presence of lymph node metastases, since lymphatic metastatic spread correlates with a significant decrease in the survival rate of patients. […] While primary risk factors are tobacco use and alcohol consumption, the role of the oncogenic human papillomaviruses (HPVs) has been implicated in HNSCC as well and many studies have suggested HPV infection as a risk factor of the HNSCC development. […] The infiltration of TAMs is a major contributor to the inflammation in HNSCC and is associated with poor prognosis, lymph node metastasis and low survival. […] The growth of primary tumor is associated with the presence of immune cells, which cause inflammation frequently observed in HNSCC. […] Several studies investigated the significance of the overall population of tumor-infiltrating lymphocytes (TILs) as a prognostic marker of HNSCC.

• #77 Effect of tumor microenvironment on pathogenesis of the head and neck squamous cell carcinoma: a systematic review | Molecular Cancer | Full Text

  https://molecular-cancer.biomedcentral.com/articles/10.1186/s12943-019-0983-5

  The most important prognostic determinant of HNSCC tumors is considered the presence of lymph node metastases, since lymphatic metastatic spread correlates with a significant decrease in the survival rate of patients. […] While primary risk factors are tobacco use and alcohol consumption, the role of the oncogenic human papillomaviruses (HPVs) has been implicated in HNSCC as well and many studies have suggested HPV infection as a risk factor of the HNSCC development. […] The infiltration of TAMs is a major contributor to the inflammation in HNSCC and is associated with poor prognosis, lymph node metastasis and low survival. […] The growth of primary tumor is associated with the presence of immune cells, which cause inflammation frequently observed in HNSCC. […] Several studies investigated the significance of the overall population of tumor-infiltrating lymphocytes (TILs) as a prognostic marker of HNSCC.

• #78 Effect of tumor microenvironment on pathogenesis of the head and neck squamous cell carcinoma: a systematic review | Molecular Cancer | Full Text

  https://molecular-cancer.biomedcentral.com/articles/10.1186/s12943-019-0983-5

  The loss of E-cadherin and high vimentin levels have been associated with tumor progression and an increase of metastases in HNSCC patients. […] The expression of MMPs commonly overexpressed in HNSCC include MMP-1, MMP-2, MMP-3, MMP-7, MMP-8, MMP-9, MMP-10, MMP-11, MMP-13, and MT1-MMP. […] The expression of secreted MMP-1, MMP-2, MMP-9 and transmembrane protease membrane type 1 MMP are commonly associated with HNSCC progression. […] The expression of MMP-2 and MMP-9 levels have been reported in correlation with local invasion, cervical nodal metastasis, tumor progression and prognosis of HNSCC patients. […] The role of CAFs in the process of EMT in many types of cancer, including HNSCC, has been intensely researched. […] The presence of CAFs promotes cancer cell invasion. […] The stimulating effect of CAFs on HNSCC invasion has been described by various in vitro assays.

• #79 Effect of tumor microenvironment on pathogenesis of the head and neck squamous cell carcinoma: a systematic review | Molecular Cancer | Full Text

  https://molecular-cancer.biomedcentral.com/articles/10.1186/s12943-019-0983-5

  The loss of E-cadherin and high vimentin levels have been associated with tumor progression and an increase of metastases in HNSCC patients. […] The expression of MMPs commonly overexpressed in HNSCC include MMP-1, MMP-2, MMP-3, MMP-7, MMP-8, MMP-9, MMP-10, MMP-11, MMP-13, and MT1-MMP. […] The expression of secreted MMP-1, MMP-2, MMP-9 and transmembrane protease membrane type 1 MMP are commonly associated with HNSCC progression. […] The expression of MMP-2 and MMP-9 levels have been reported in correlation with local invasion, cervical nodal metastasis, tumor progression and prognosis of HNSCC patients. […] The role of CAFs in the process of EMT in many types of cancer, including HNSCC, has been intensely researched. […] The presence of CAFs promotes cancer cell invasion. […] The stimulating effect of CAFs on HNSCC invasion has been described by various in vitro assays.

• #80 Effect of tumor microenvironment on pathogenesis of the head and neck squamous cell carcinoma: a systematic review | Molecular Cancer | Full Text

  https://molecular-cancer.biomedcentral.com/articles/10.1186/s12943-019-0983-5

  The possible contribution of CAFs to the EMT induction in HNSCC carcinoma cells has been implicated by immunohistochemical analyses, in which markers associated with EMT in CAFs in paired primary and metastatic OSCC showed that Ki-67+ metastatic carcinoma cells downregulate E-cadherin when in direct contact with CAFs. […] It has been reported that expressions of EMT promoters, Snail, Slug, TWIST and SMAD nuclear interacting protein-1(SNIP1), which are regulated by HIF-1, correlate with induction of EMT phenotype in OSCC cells in vitro. […] A study by Huang et al. reported that SLUG regulated the expression of MT4-MMP under hypoxia, which promoted the invasiveness of HNSCC cell lines. […] It has been suggested that hypoxia induces EMT in OSCC via activation of the Notch signaling pathway and the inhibition of the Notch signaling pathway suppresses EMT.

• #81 Effect of tumor microenvironment on pathogenesis of the head and neck squamous cell carcinoma: a systematic review | Molecular Cancer | Full Text

  https://molecular-cancer.biomedcentral.com/articles/10.1186/s12943-019-0983-5

  The possible contribution of CAFs to the EMT induction in HNSCC carcinoma cells has been implicated by immunohistochemical analyses, in which markers associated with EMT in CAFs in paired primary and metastatic OSCC showed that Ki-67+ metastatic carcinoma cells downregulate E-cadherin when in direct contact with CAFs. […] It has been reported that expressions of EMT promoters, Snail, Slug, TWIST and SMAD nuclear interacting protein-1(SNIP1), which are regulated by HIF-1, correlate with induction of EMT phenotype in OSCC cells in vitro. […] A study by Huang et al. reported that SLUG regulated the expression of MT4-MMP under hypoxia, which promoted the invasiveness of HNSCC cell lines. […] It has been suggested that hypoxia induces EMT in OSCC via activation of the Notch signaling pathway and the inhibition of the Notch signaling pathway suppresses EMT.

• #82 Effect of tumor microenvironment on pathogenesis of the head and neck squamous cell carcinoma: a systematic review | Molecular Cancer | Full Text

  https://molecular-cancer.biomedcentral.com/articles/10.1186/s12943-019-0983-5

  The possible contribution of CAFs to the EMT induction in HNSCC carcinoma cells has been implicated by immunohistochemical analyses, in which markers associated with EMT in CAFs in paired primary and metastatic OSCC showed that Ki-67+ metastatic carcinoma cells downregulate E-cadherin when in direct contact with CAFs. […] It has been reported that expressions of EMT promoters, Snail, Slug, TWIST and SMAD nuclear interacting protein-1(SNIP1), which are regulated by HIF-1, correlate with induction of EMT phenotype in OSCC cells in vitro. […] A study by Huang et al. reported that SLUG regulated the expression of MT4-MMP under hypoxia, which promoted the invasiveness of HNSCC cell lines. […] It has been suggested that hypoxia induces EMT in OSCC via activation of the Notch signaling pathway and the inhibition of the Notch signaling pathway suppresses EMT.

• #83 Effect of tumor microenvironment on pathogenesis of the head and neck squamous cell carcinoma: a systematic review | Molecular Cancer | Full Text

  https://molecular-cancer.biomedcentral.com/articles/10.1186/s12943-019-0983-5

  The results also implicate that the invasive phenotype of cancer cells is regulated by cell contact-dependent hypoxia-mediated Notch signaling coupled with the paracrine activation of the EGFR, which is mediated by the ADAM12-dependent secretion of HB-EGF. […] The study showed that hypoxia increased the expression levels of genes associated with glycolysis, such as MCT1, MCT4, GLUT1 and LDHA in HNSCC cells and stimulated uptake of glucose, production of lactate and cell invasion in vitro. […] The mechanisms of extravasation of tumor cells have been well described in many types of cancer; however, the effect of microenvironmental factors on extravasation in HNSCC has yet to be investigated.

• #84 Effect of tumor microenvironment on pathogenesis of the head and neck squamous cell carcinoma: a systematic review | Molecular Cancer | Full Text

  https://molecular-cancer.biomedcentral.com/articles/10.1186/s12943-019-0983-5

  The loss of E-cadherin and high vimentin levels have been associated with tumor progression and an increase of metastases in HNSCC patients. […] The expression of MMPs commonly overexpressed in HNSCC include MMP-1, MMP-2, MMP-3, MMP-7, MMP-8, MMP-9, MMP-10, MMP-11, MMP-13, and MT1-MMP. […] The expression of secreted MMP-1, MMP-2, MMP-9 and transmembrane protease membrane type 1 MMP are commonly associated with HNSCC progression. […] The expression of MMP-2 and MMP-9 levels have been reported in correlation with local invasion, cervical nodal metastasis, tumor progression and prognosis of HNSCC patients. […] The role of CAFs in the process of EMT in many types of cancer, including HNSCC, has been intensely researched. […] The presence of CAFs promotes cancer cell invasion. […] The stimulating effect of CAFs on HNSCC invasion has been described by various in vitro assays.

• #85 Effect of tumor microenvironment on pathogenesis of the head and neck squamous cell carcinoma: a systematic review | Molecular Cancer | Full Text

  https://molecular-cancer.biomedcentral.com/articles/10.1186/s12943-019-0983-5

  The infiltration of TAMs is a major contributor to the inflammation in HNSCC and is associated with poor prognosis, lymph node metastasis and low survival. […] Immunohistochemical analyses of primary OSCC report higher density of CAFs in over 60% cases, while healthy tissues and adjacent stroma of premalignant lesions show no staining. […] It has been observed that increased numbers of CAFs within the primary tumor correlate with worse prognosis of HNSCC patients. […] The major ECM proteins involved in HNSCC development and progression are collagen, laminin and fibronectin. […] The expression of secreted MMP-1, MMP-2, MMP-9 and transmembrane protease membrane type 1 MMP are commonly associated with HNSCC progression. […] The activity of MMPs is regulated by tissue inhibitors of metalloproteases (TIMPs), secreted mainly by fibroblasts in the stroma.

• #86 Effect of tumor microenvironment on pathogenesis of the head and neck squamous cell carcinoma: a systematic review | Molecular Cancer | Full Text

  https://molecular-cancer.biomedcentral.com/articles/10.1186/s12943-019-0983-5

  The loss of E-cadherin and high vimentin levels have been associated with tumor progression and an increase of metastases in HNSCC patients. […] The expression of MMPs commonly overexpressed in HNSCC include MMP-1, MMP-2, MMP-3, MMP-7, MMP-8, MMP-9, MMP-10, MMP-11, MMP-13, and MT1-MMP. […] The expression of secreted MMP-1, MMP-2, MMP-9 and transmembrane protease membrane type 1 MMP are commonly associated with HNSCC progression. […] The expression of MMP-2 and MMP-9 levels have been reported in correlation with local invasion, cervical nodal metastasis, tumor progression and prognosis of HNSCC patients. […] The role of CAFs in the process of EMT in many types of cancer, including HNSCC, has been intensely researched. […] The presence of CAFs promotes cancer cell invasion. […] The stimulating effect of CAFs on HNSCC invasion has been described by various in vitro assays.

• #87 Effect of tumor microenvironment on pathogenesis of the head and neck squamous cell carcinoma: a systematic review | Molecular Cancer | Full Text

  https://molecular-cancer.biomedcentral.com/articles/10.1186/s12943-019-0983-5

  The infiltration of TAMs is a major contributor to the inflammation in HNSCC and is associated with poor prognosis, lymph node metastasis and low survival. […] Immunohistochemical analyses of primary OSCC report higher density of CAFs in over 60% cases, while healthy tissues and adjacent stroma of premalignant lesions show no staining. […] It has been observed that increased numbers of CAFs within the primary tumor correlate with worse prognosis of HNSCC patients. […] The major ECM proteins involved in HNSCC development and progression are collagen, laminin and fibronectin. […] The expression of secreted MMP-1, MMP-2, MMP-9 and transmembrane protease membrane type 1 MMP are commonly associated with HNSCC progression. […] The activity of MMPs is regulated by tissue inhibitors of metalloproteases (TIMPs), secreted mainly by fibroblasts in the stroma.

• #88

  https://grantome.com/grant/NIH/R01-DE027329-01

  It is crucial to better understand immune evasion mechanisms in head and neck cancers in order to enhance their susceptibility to immunotherapy. About 90% of head and neck cancers are squamous cell carcinomas (HNSCC). Recurrent or metastatic HNSCCs are being treated with checkpoint blockade immunotherapy targeting programmed death 1 (PD-1), a co-inhibitory receptor on T cells. However, only a subset of HNSCC patients responded to such anti-PD-1 therapy (10-20%). Thus, there is an urgent need to elucidate mechanisms underlying therapy unresponsiveness to single blockade of PD-1. […] HNSCC development often associates with oncogenic mutations, such as heterozygous loss of Smad4, gain-of-function mutations of PIK3CA or loss-of-function mutations of Notch1. It remains largely unknown how HNSCCs evade immune recognition. To address this question, we performed studies with a transplanted SCC model caused by combining KrasG12D mutation and Smad4 loss (termed KRS-SCC). We found that KRS-SCC tumors completely escaped T cell-mediated anti-tumor responses, manifested with exhausted CD8 and CD4 TILs co-expressing PD-1 and LAG-3. Consistently, dual inhibition of PD-1 and LAG-3 suppressed the growth of KRS-SCCs. We propose to employ our unique mouse models and human patient samples to further elucidate immune evasion mechanisms of HNSCCs. Our proposed studies may substantially advance our understanding in mechanisms that underlie therapy failure of single PD-1 blockade.

• #89

  https://grantome.com/grant/NIH/R01-DE027329-01

  It is crucial to better understand immune evasion mechanisms in head and neck cancers in order to enhance their susceptibility to immunotherapy. About 90% of head and neck cancers are squamous cell carcinomas (HNSCC). Recurrent or metastatic HNSCCs are being treated with checkpoint blockade immunotherapy targeting programmed death 1 (PD-1), a co-inhibitory receptor on T cells. However, only a subset of HNSCC patients responded to such anti-PD-1 therapy (10-20%). Thus, there is an urgent need to elucidate mechanisms underlying therapy unresponsiveness to single blockade of PD-1. […] HNSCC development often associates with oncogenic mutations, such as heterozygous loss of Smad4, gain-of-function mutations of PIK3CA or loss-of-function mutations of Notch1. It remains largely unknown how HNSCCs evade immune recognition. To address this question, we performed studies with a transplanted SCC model caused by combining KrasG12D mutation and Smad4 loss (termed KRS-SCC). We found that KRS-SCC tumors completely escaped T cell-mediated anti-tumor responses, manifested with exhausted CD8 and CD4 TILs co-expressing PD-1 and LAG-3. Consistently, dual inhibition of PD-1 and LAG-3 suppressed the growth of KRS-SCCs. We propose to employ our unique mouse models and human patient samples to further elucidate immune evasion mechanisms of HNSCCs. Our proposed studies may substantially advance our understanding in mechanisms that underlie therapy failure of single PD-1 blockade.

• #90 Scientists uncover a mechanism that could lead to new immunotherapies head and neck cancer

  https://medicalxpress.com/news/2020-03-scientists-uncover-mechanism-immunotherapies-neck.html

  Researchers at UC have discovered a previously unknown mechanism that could explain the reason behind decreased immune function in cancer patients and could be a new therapeutic target for immunotherapy for those with head and neck cancers. […] Led by Laura Conforti, professor in the Department of Nephrology and Hypertension at the UC College of Medicine, the team discovered that a reduced interaction between a molecule called calmodulin and an ion channel (KCa3.1) in the immune cells of cancer patients plays an important role in the reduced function of these cells. […] „Identifying the mechanism of this underlying dysfunction can help us identify molecules that we can target with drugs and ultimately restore the ability of these cells to enter and kill the tumors,” says Conforti. […] „In this study, we were able to show that the function of these channels in T-cells from cancer patients is decreased which results in a decreased T-cell accumulation in solid tumors,” Conforti says.

• #91 Scientists uncover a mechanism that could lead to new immunotherapies head and neck cancer

  https://medicalxpress.com/news/2020-03-scientists-uncover-mechanism-immunotherapies-neck.html

  „As previously stated, the channels do not function if the calmodulin does not bind to them. Thus, the decreased calmodulin binding in T-cells from cancer patients results in decreased function and leads to reduced tumor infiltration and killing of the cancer cells.” […] „These findings strengthen the therapeutic potentials of [these] activators, which could restore cytotoxic T-cell functionality and can ultimately lead to additional immunotherapeutic options for patients with cancer,” Conforti adds.

• #92

  https://medschool.cuanschutz.edu/colorado-cancer-center/research/head-and-neck-cancer-spore

  The Colorado Head and Neck Cancer SPORE takes advantage of our expertise in basic and clinical sciences and uses unique model systems to identify novel molecular and cellular mechanisms of Colorado Head and Neck Cancer pathogenesis targetable by therapeutic interventions to treat all cancer types arising from head and neck anatomic sites. […] This project will study if RT-upregulated EFNB2 on tumor vascular endothelial cells act preferentially to recruit EphB4+ T regulatory cells (Tregs) and monocytes (precursors of tumor-associated macrophages, TAMs) for bi-directional signaling. […] This project will test the hypothesis that dual inhibition of TGFb/PD-L1 as a new immunotherapy combined with RT induces in situ vaccination, reverses immune suppression, and overcomes RT resistance via both T cell-dependent and -independent mechanisms.

• #93 Medical Science Monitor | Dual role of VEGF family members in the pathogenesis of head and neck cancer(HNSCC): possible link between angiogenesis and immune tolerance. – Article abstract #201014

  https://medscimonit.com/abstract/index/idArt/201014

  Dual role of VEGF family members in the pathogenesis of head and neck cancer(HNSCC): possible link between angiogenesis and immune tolerance. […] Some of the angiogenic factors released by tumor and stroma cells, including vascular endothelial growth factor (VEGF), are thought to affect DC function. […] Increased expression of VEGF-A and VEGF-C was found in tumor tissues compared to normal epithelium (P=0.001). […] However, VEGF-D levels were decreased in patients with cervical nodal metastasis as compared to patients with negative lymph node status. […] Multivariate analysis demonstrated that VEGF-A correlated with microvessel density (P=0.01), disease progression (P=0.038), a reduced number of local and peripheral mature dendritic cells (DC) (P=0.015) and an increased number of peripheral immature DCs (P=0.05). […] Taken together, our results identify VEGF-A as a multifunctional factor involved in angiogenesis, tumor progression, immunosuppression and immune tolerance.

• #94 Research progress on the role and mechanism of circular RNA in drug resistance of head and neck squamous cell carcinoma

  https://www.oaepublish.com/articles/cdr.2024.57

  Drug resistance in tumors constitutes a significant obstacle to tumor therapy. Head and neck squamous cell carcinoma (HNSCC) presents a major challenge due to its deep anatomical location, limited space, and complex structure. […] Recent advances in high-throughput sequencing and bioinformatics technology revealed that circRNAs participate in tumor proliferation, invasion, migration, and drug resistance. […] A better understanding of the association between circRNAs and HNSCC will help us to more effectively study and explore new early diagnostic indicators and therapeutic targets for HNSCC. This review aims to clarify the role of circRNAs in drug resistance in HNSCC and its potential as a diagnostic and therapeutic target. […] circRNAs are involved in this process. For example, overexpression of circ-000543 in radioinsensitive NPC contributes to the development of radioresistance. This circRNA functions by binding to miR-9, thereby upregulating platelet-derived growth factor receptor B (PDGFRB) expression.

• #95 Molecular mechanism(s) of regulation(s) of c-MET/HGF signaling in head and neck cancer | Molecular Cancer | Full Text

  https://molecular-cancer.biomedcentral.com/articles/10.1186/s12943-022-01503-1

  An aberrant HGF/c-MET signaling can lead to uncontrolled proliferation, motility, invasiveness, and angiogenesis and can play an essential role in the development, progression and survival of cancer including head and neck squamous cell carcinoma (HNSCC). […] HNSCC is the sixth most common cancer worldwide. It develops from the mucosal epithelium in the oral cavity, pharynx, larynx and are the most common malignancies that takes place in the head and neck. The common practices or risk factors that has been associated with HNSCC are smoking, excessive alcohol consumption, or both. […] Increased expression of receptor tyrosine kinases such as HER-2 and MET which can lead to resistance towards EGFR mediated therapy against HNSCC. […] c-MET is expressed in all stages, with having high expression in N2 and N3 nodal metastasis.

• #96 Molecular mechanism(s) of regulation(s) of c-MET/HGF signaling in head and neck cancer | Molecular Cancer | Full Text

  https://molecular-cancer.biomedcentral.com/articles/10.1186/s12943-022-01503-1

  c-MET pathway has been reported to be associated with several other signaling pathways in HNSCC. […] c-MET signaling is also known to contribute widely in metabolic reprogramming of tumor cells. […] The c-MET/HGF signaling is also known to contribute widely in metabolic reprogramming of tumor cells. Increased glucose metabolism is highly preferred by cancer cells to yield much higher ATP and it also generates biosynthesis relevant precursor molecules. […] Chemoresistance towards EGFR inhibition by small molecule tyrosine kinase inhibitors such as gefitinib or erlotinib are common features in clinical trials. Upregulation of c-MET has also reported its contribution towards cetuximab resistance in HNSCC patients. […] c-MET has a major contribution towards compensating for inhibition of RTK pathways that help in proliferation and metastasis in HNSCC. Therefore, targeting c-MET along with other receptor tyrosine kinases can bring effective therapeutic strategies.

• #97 Research progress on the role and mechanism of circular RNA in drug resistance of head and neck squamous cell carcinoma

  https://www.oaepublish.com/articles/cdr.2024.57

  The emergence of multidrug resistance in tumor cells is the main reason for chemotherapy failure. […] With the extensive investigation of circRNA biological function, increasing evidence suggests that certain circRNAs are significantly upregulated in drug-resistant HNSCC tissues. Furthermore, circRNAs are closely associated with some signaling pathways that are involved in drug resistance of HNSCC, such as PI3K/AKT, MAPK, NF-B, and Wnt/-catenin signaling pathways. […] These circRNAs can act as „sponges” for miRNAs by containing multiple miRNA binding sites, thereby adsorbing and inhibiting miRNA activity and subsequently regulating downstream pathways that affect tumor sensitivity to drugs. […] Specific circRNAs have been reported to play a role in metastasis and resistance to chemotherapy in NPC.

• #98 Research progress on the role and mechanism of circular RNA in drug resistance of head and neck squamous cell carcinoma

  https://www.oaepublish.com/articles/cdr.2024.57

  The emergence of multidrug resistance in tumor cells is the main reason for chemotherapy failure. […] With the extensive investigation of circRNA biological function, increasing evidence suggests that certain circRNAs are significantly upregulated in drug-resistant HNSCC tissues. Furthermore, circRNAs are closely associated with some signaling pathways that are involved in drug resistance of HNSCC, such as PI3K/AKT, MAPK, NF-B, and Wnt/-catenin signaling pathways. […] These circRNAs can act as „sponges” for miRNAs by containing multiple miRNA binding sites, thereby adsorbing and inhibiting miRNA activity and subsequently regulating downstream pathways that affect tumor sensitivity to drugs. […] Specific circRNAs have been reported to play a role in metastasis and resistance to chemotherapy in NPC.

• #99 Research progress on the role and mechanism of circular RNA in drug resistance of head and neck squamous cell carcinoma

  https://www.oaepublish.com/articles/cdr.2024.57

  circCRIM1 is abundantly expressed in NPC tissues with high metastasis and can enhance forkhead box Q1 (FOXQ1) expression by targeting miR-422a. This, in turn, promotes NPC metastasis and confers resistance to docetaxel chemotherapy. […] circPARD3 promotes cisplatin resistance of NPC side population cells. This effect is mediated through the miR-579-3p/SIRT1/SSRP1 axis. […] Some circRNAs show significant differential expression between chemotherapy-resistant OSCC patients and corresponding normal tissues. […] As a miRNA sponge for miR-1252, circ-ILF2 inhibits miR-1252 expression. miR-1252 regulates the expression of Krppel-like factor 8 (KLF8), which functions on proliferation, drug resistance, and inflammation of OSCC, thereby promoting cisplatin resistance. […] The circRNA circANKS1B (circ-0007294), originating from exons 5 to 8 of the ANKS1B gene, is positively associated with the expression of transforming growth factor-1 (TGF-1) in OSCC tissues. circANKS1B facilitates the growth and resistance of OSCC by stimulating the TGF- signaling pathway in oral cancer cells. […] Overall, research on chemotherapy for HNSCC is progressing with the hope of finding more effective treatments to improve the patients survival rate and quality of life. However, a significant number of HNSCC patients exhibit chemotherapy resistance, posing a major challenge to effective treatment.

• #100 Research progress on the role and mechanism of circular RNA in drug resistance of head and neck squamous cell carcinoma

  https://www.oaepublish.com/articles/cdr.2024.57

  circCRIM1 is abundantly expressed in NPC tissues with high metastasis and can enhance forkhead box Q1 (FOXQ1) expression by targeting miR-422a. This, in turn, promotes NPC metastasis and confers resistance to docetaxel chemotherapy. […] circPARD3 promotes cisplatin resistance of NPC side population cells. This effect is mediated through the miR-579-3p/SIRT1/SSRP1 axis. […] Some circRNAs show significant differential expression between chemotherapy-resistant OSCC patients and corresponding normal tissues. […] As a miRNA sponge for miR-1252, circ-ILF2 inhibits miR-1252 expression. miR-1252 regulates the expression of Krppel-like factor 8 (KLF8), which functions on proliferation, drug resistance, and inflammation of OSCC, thereby promoting cisplatin resistance. […] The circRNA circANKS1B (circ-0007294), originating from exons 5 to 8 of the ANKS1B gene, is positively associated with the expression of transforming growth factor-1 (TGF-1) in OSCC tissues. circANKS1B facilitates the growth and resistance of OSCC by stimulating the TGF- signaling pathway in oral cancer cells. […] Overall, research on chemotherapy for HNSCC is progressing with the hope of finding more effective treatments to improve the patients survival rate and quality of life. However, a significant number of HNSCC patients exhibit chemotherapy resistance, posing a major challenge to effective treatment.

• #101 Molecular pathways and targeted therapies in head and neck cancers pathogenesis

  https://ouci.dntb.gov.ua/en/works/4OoYJ1j4/

  Molecular pathways and targeted therapies in head and neck cancers pathogenesis […] The substantial heterogeneity exhibited by head and neck cancer (HNC), encompassing diverse cellular origins, anatomical locations, and etiological contributors, combined with the prevalent late-stage diagnosis, poses significant challenges for clinical management. Genomic sequencing endeavors have revealed extensive alterations in key signaling pathways that regulate cellular proliferation and survival. […] Enhanced comprehension of the genomic and immunological landscapes characteristic of HNC is anticipated to facilitate a more rigorous assessment of targeted therapies benefits and limitations, optimize their clinical deployment, and foster innovative advancements in treatment approaches. This review presents an update on the molecular mechanisms and mutational spectrum of HNC driving the oncogenesis of head and neck malignancies and explores their implications for advancing diagnostic methodologies and precision therapeutics.

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